Multiple Sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS), affecting an estimated 400,000 people in the U.S. and 2 million people worldwide. It is the leading cause of neurological disability in young and middle-aged adults. MS causes both cognitive and physical disability that frequently leads to unemployment, and thus is a major health concern with considerable economic consequences. Diagnosis of MS is generally achieved by a combination of clinical assessments of cognitive and physical impairment followed by magnetic resonance imaging (MRI) of the brain. Clinically, dynamic-contrast-enhanced MRI (DCE-MRI) is used to identify acute white matter lesions. Lesions appearing in white matter are well characterized and easily imaged by MRI, but white matter lesion load (total volume of lesions relative to total brain volume) is not indicative of clinical disability. Recent studies indicate that grey matter (GM) degeneration and cortical lesions are closely related to cognitive decline in MS. However, current protocols are not designed to image lesions and diffuse tissue damage in the cortex. Novel imaging techniques are needed to characterize GM changes in-vivo in MS. Pharmacokinetic (PK) modeling of DCE-MRI data yields physiologically important parameters such as blood volume, vascular and blood-brain barrier (BBB) permeability, and transendothelial water exchange. The work proposed in this research project will provide minimally invasive means of measuring and monitoring physiological changes in cortical GM in-vivo. Physiological and vascular changes in cortical GM associated with MS disease progression will be identified and quantified. Hypothesis: The physiologically relevant PK parameters will detect and quantify in-vivo cortical GM vascular and physiological changes associated with MS. Angiogenesis (indicated by increased blood volume) and BBB permeability will both be elevated in MS compared to healthy controls. Human data collected on our 7 Tesla MRI instrument will be used to test this hypothesis in two phases: (1) Cross-sectional study of regional and global tissue vascular microenvironment differences in cortical GM between healthy Control and MS subjects; (2) the technical refinement of 7T MRI sequences and protocols that take advantage of a recently acquired 24-channel 300 MHz head RF coil. The second phase will develop novel imaging techniques to obtain robust and clinically feasible DCE-MRI measurements in the human cortex.